The focus of this proposal is on the cardiovascular factors which are responsible for the dynamic changes in respiratory gas exchange (oxygen uptake and carbon dioxide output) occurring in response to a sudden increase in metabolic rate. We plan to determine the mechanisms responsible for the normal gas exchange and heart rate responses induced by exercise, the magnitude and range of these responses, and the alterations in responses brought about by abnormalities in the pulmonary circulation. It is well appreciated that in the steady state, measurements of oxygen uptake in the lungs (VO2) reflect the level of oxygen consumption, or metabolic rate, at the cellular level. Much of daily living is not steady state, however, but a series of different and varied activity levels with different energy requirements. In the unsteady state following transition from one activity level to another, the cardiovascular and respiratory systems must adjust appropriately to satisfy the changed metabolic requirements of the tissues. Analysis of the unsteady state can therefore provide information about the function of the cardiac and respiratory systems and their control mechanisms. The basis for such analysis is the Fick relationship which states that VO2 is equal to the product of pulmonary blood flow and the arteriovenous difference in O2 content across the pulmonary circulation. The dynamic changes in VO2 are likewise dependent on the rate, pattern, and magnitude of change of these factors. Because the immediate determinants of VO2 kinetics are changes occurring in the pulmonary circulation, this analysis has particular potential for providing important information regarding the functional state of the pulmonary vasculature. The proposed work is significant both because of the insights to be gained regarding normal cardiovascular function and because of the potential of providing a unique, noninvasive means of evaluating patients with pulmonary vascular disease. The principle investigator has training in respiratory medicine and exercise physiology and has done preliminary studies of the gas exchange response to exercise in patients with cyanotic congenital heart disease. The proposed work makes use of the sponsor's extensive expertise in exercise and respiratory physiology, and the laboratory's unique technical capabilities for breath-by-breath determination of alveolar gas exchange.